Join the Society for Biomaterials for their last meeting of the semester today, December 4 at 5 p.m. in Maryland Hall room 109 on the Homewood campus of Johns Hopkins University. Honggang Cui, assistant professor of chemical and biomolecular engineering, will present “How Nano Impacts Medicine.” Refreshments will be served. Cui is an affiliated faculty member of Johns Hopkins Institute for NanoBioTechnology.

Here is an abstract for Dr. Cui’s talk:

Honggang Cui

From the dawn of civilization, humans have recognized the therapeutic effect of some natural herbs, and the use of plants as therapeutic agents is a long-standing practice throughout the human history. However, the major advance in medicine did not start until the mid-19th century when the active compounds could be actually isolated, purified and identified. The identification of the active compound and its pharmacophore allows not only for the administration of drugs with a known dose, but more importantly for the synthesis of modified drugs with improved efficacy.

Nowadays, modern pharmacology has become part of our daily living, greatly improving the quality of life and transforming the way we live. However, there are still many incurable diseases, such as cancer, that medicine has yet to provide a solution. The emergence of nanotechnology as a field in 1980s has impacted many scientific disciplines including medicine. In particular, nanotechnology-based medicine has entered clinical use over the past two decades.

Can nano help provide a revolutionary solution to cancer? And how could the uses of nano improve the current clinical practice in cancer treatments? This lecture will provide a brief overview of the impact that nanotechnology could have on medicine.

Editor’s Note: The following is a summary of one of the talks from the 2013 Nano-bio Symposium hosted by Johns Hopkins Institute for NanoBioTechnology held May 17. This summary was written by Christian Pick, a doctoral candidate in the chemical and biomolecular engineering laboratory of Joelle Frechette. Look for other symposium summaries on the INBT blog.

One of the greatest promises of merging nanotechnology with medicine is in the creation of highly selective vehicles for drug delivery based on nanoparticles. However, translating nanoparticles into commercialized medical products comes with many challenges. Anthony Tuesca, a scientist in the Innovative Drug Delivery Group at MedImmune, outlined a number of these challenges and ways to address them.

Research in nanotechnology begins at the lab bench, often without much thought given to future commercialization. But commercialization is a huge undertaking. In between the lab-bench and final product there is a whole litany of challenges that must be tackled. One such challenge lies in scaling up processes for production. As Tuesca stated, for scale-up to be viable, laboratory processes must be compatible with current manufacturing capabilities.

Another challenge is navigating an often confusing regulatory landscape. Although nanoparticle based therapies don’t necessarily invoke harsher requirements than conventional medical treatments (in that both require clinical trials that demonstrate safety and efficacy) more complex technology requires more proof of effectiveness. Interestingly, Tuesca mentions that the U.S. Food and Drug Administration currently lacks an official definition of nanotechnology.

Ultimately, Tuesca’s presentation urges researchers to take a proactive role in translating laboratory discoveries into viable medical technology. Such a role requires researchers to consider future commercialization early in their research and act accordingly.

Mark your calendar. Those affiliated with Johns Hopkins Institute for NanoBioTechnology or Center for Cancer Nanotechnology Excellence may be interested to know that online registration is now open for the 2013 International Conference of RNA Nanotechnology and Therapeutics to be held in Lexington, KY on April 3-5, 2013 at the Crowne Plaza Hotel & Resorts. The meeting is organized by Peixuan Guo (University of Kentucky CNPP), John Rossi (Beckman Research Institute), Bruce Shapiro (NCI), and Neocles Leontis (Bowling Green State University). Along with invited speakers, there will also be a poster session. Invited speakers are yet to be announced.

Research does not take a holiday during the summer at Johns Hopkins University in Baltimore, Md. In fact, it ramps up with the addition of many new faces from across the country.

The Johns Hopkins Institute for NanoBioTechnology summer research interns have arrived and are already busy at work in various laboratories. This year’s group is the largest the institute has ever hosted, with 17 undergraduates from universities nationwide.

Of the total, three students are affiliated with the Center of Cancer Nanotechnology Excellence and four are affiliated with the Physical Sciences-Oncology Center. The remaining 10 are part of the National Science Foundation Research Experience for Undergraduates program. All are hosted through INBT, which serves as a hub for their academic and social activities.

INBT summer interns conduct 10 weeks of research in a laboratory either on the Homewood or the medical campus of the University. At the end of that time, students have learned how to work in a multidisciplinary team and how to manage a short term research project. They also discover if research is a pathway they want to pursue after earning their bachelor’s degrees.

In August, interns from many of the science, medicine, engineering and public health summer programs will gather for a poster session to be held on August 2 at 3 p.m. in Turner Concourse. The poster session will allow students to show off the results of their their work.

This year’s INBT/PS-OC/CCNE interns include:

At the Whiting School of Engineering…

Amani Alkayyali from Wayne State University is an REU student in the laboratory of Honggang Cui assistant professor in the Department of Chemical and Biomolecular Engineering. Also in the Cui lab are CCNE intern Matthew Fong from the University of California, Berkeley and Michelle LaComb, an REU student from Rice University.

Sharon Gerecht, assistant professor in the Department of Chemical and Biomolecular engineering, is hosting three interns. Josh Porterfield of Cornell University and Carolyn Zhang from the University of California, San Diego are both PS-OC interns, and Bria Macklin of Howard University is an REU intern.

Jacqueline Carozza of Cornell University is a PS-OC student working in the lab of Denis Wirtz, professor in the Department Chemical and Biomolecular Engineering. Cassandra Loren from Oregon State University is a PS-OC intern also working in the Wirtz lab.

Eric Do from the University of Washington is an REU working in the lab of assistant professor Margarita Herrara-Alonso in the Department of Materials Science and Engineering.

Olivia Hentz from Cornell is an REU student working in the lab of Jonah Erlebacher, professor in the Department of Materials Science and Engineering.

Justin Samorajski from the University of Dallas is a returning summer intern, once again working in the materials science and engineering lab of professor Peter Searson as part of the CCNE.

At the School of Medicine…

Lauren Lee of Cornell University is an REU working in the lab of biomedical engineering lab of associate professor Hai-Quan Mao.

Albert Lu from the University of California Berkeley is a CCNE intern working in the biomedical engineering lab of associate professor Jeff Wang.

Bianca Lascano from Norfolk State University is an REU in assistant professor Jordan Green’s biomedical engineering lab.

Charlie Nusbaum of the Richard Stockton College is an REU intern in the radiation oncology lab of assistant professor Robert Ivkov.

At the Krieger School of Arts and Sciences…

Anthony Loder of Rowan University is an REU working in the biology lab of assistant professor Xin Chen.

Daniel McClelland is also REU from Bethany College works in the chemistry laboratory of professor Howard Fairbrother.

Nanotechnology, regenerative medicine and cancer will be the topic of a special biomedical engineering seminar on March 6 at 3 p.m. in the Darner Conference Room, Ross Building, Room G007 at the Johns Hopkins School of Medicine. Speaker Sangeeta Bhatia, MD, PhD, director, of the Laboratory for Multiscale Regenerative Technologies at Massachusetts Institute of Technology will present “It’s a small world: Micro/Nanotechnology in Regenerative Medicine and Cancer. ” She will discuss the role of micro and nanotechnology for mimicking, monitoring and perturbing the tissue microenvironment.

“I will present our work on reconstructing normal liver microenvironments using microtechnology, biomaterials and induced pluripotent stem cells as well as our work on normalizing diseased cancer microenvironments using both inorganic and organic nano materials,” Bhatia noted in an announcement. Bhatia is a professor of Health Sciences and Technology and professor of Electrical Engineering and Computer Science at MIT.

The talk is hosted by associate professor of Materials Science and Engineering and affiliated faculty member of the Institute for NanoBioTechnology Hai-Quan Mao. The event is free and open to the Johns Hopkins Community. Refreshments will be served.

Close-up of a cylindrically-shaped microfluidic device with two fluorescent solutions flowing through. Reproduced with permission from Nature Communications.

A leaf works something like a miniature laboratory. While the pores on the leaf surface allow it to channel nutrients in and waste products away from a plant, part of a leaf’s function also lies in its ability to curl and twist. Engineers use polymers to create their own mini-labs, devices called “labs-on-a-chip,” which have numerous applications in science, engineering and medicine. The typical flat, lab on a chip, or microfluidic device, resembles an etched microscopy cover slip with channels and grooves.

But what if you could get that flat lab-on-a-chip to self-assemble into a curve, mimicking the curl, twist or spiral of a leaf? Mustapha Jamal, a PhD student and IGERT fellow from Johns Hopkins Institute for NanoBioTechnology, has created a way to make that so.

Jamal is the lead author on “Differentially photo-crosslinked polymers enable self-assembling microfluidics,” published November 8, 2011 in Nature Communications. Along with principle investigator David Gracias, associate professor of Chemical and Biomolecular Engineering in the Whiting School of Engineering, and fellow graduate student Aasiyeh Zarafshar, Jamal has developed, for the first time, a method for creating three-dimensional lab-on-a-chip devices that can curl and twist.

The process involves shining ultraviolet (UV) light on a film of a substance called SU-8. Film areas closer to the light source become more heavily crosslinked than layers beneath, which on solvent conditioning creates a stress gradient.

Immersing the film in water causes the film to curl. Immersion in organic solvents like acetone causes the film to flatten. The curling and flattening can be reversed. The result, Jamal said, is the “self-assembly of intricate 3D devices that contain microfluidic channels.” This simple method, he added, can “program 2D polymeric (SU-8) films such that they spontaneously and reversibly curve into intricate 3D geometries including cylinders, cubes and corrugated sheets.”

Members of the Gracias lab have previously created curving and folding polymeric films consisting of two different materials. This new method achieves a stress gradient along the thickness of a single substance. “This provides considerable flexibility in the type and extent of curvature that can be created by varying the intensity and direction of exposure to UV light,” Gracias said.

Gracias explained that the method works with current protocols and materials for fabricating flat microfluidic devices. For example, one can design a 2D film with one type of lab-on-a-chip network, and then use their method to shape it into another geometry, also with microfluidic properties.

“Since our approach is compatible with planar lithography methods, we can also incorporate optical elements such as split ring resonators that have unique optical features. Alternatively, flexible electronic circuits could be incorporated and channels could be used to transport cooling fluids” Gracias said.

Tissue engineering is among the many important applications for 3D microfluidic devices, Gracias said. “Since many hydrogels can be photopolymerized, we can use the methodology of differential cross-linking to create stress gradients in these materials,” Gracias explained. “We plan to create biodegradable, vascularized tissue scaffolds using this approach.”

Biomedical engineers and clinicians at Johns Hopkins University have developed freeze-dried nanoparticles made of a shelf-stable polymer that only need the addition of water to activate their cancer-fighting gene therapy capabilities.

Principal investigator Jordan Green, assistant professor in the department of Biomedical Engineering at the Johns Hopkins School of Medicine, led the team that fabricated the polymer-based particles measuring 80 to 150 nanometers in diameter. Each particle, which is about the size of a virus, has the ability to carry a genetic cocktail designed to produce brain cancer cell-destroying molecules. After manufacture, the nanoparticles can be stored for up to 90 days before use. In principle, cancer therapies based on this technology could lead to a convenient commercial product that clinicians simply activate with water before injection into brain cancer tumor sites.

Because this method avoids the common, unpleasant side effects of traditional chemotherapy, “nanoparticle-based gene therapy has the potential to be both safer and more effective than conventional chemical therapies for the treatment of cancer,” Green said. But, he added current gene therapy nanoparticle preparations are just not practical for clinical use.

“A challenge in the field is that most non-viral gene therapy methods have very low efficacy. Another challenge with biodegradable nanoparticles, like the ones used here is that particle preparation typically takes multiple time-sensitive steps.” Green said. “Delay with formulation results in polymer degradation, and there can be variability between batches. Although this is a simple procedure for lab experiments, a clinician who wishes to use these particles during neurosurgery will face factors that would make the results unpredictable.”

In contrast, the nanoparticles developed by the Green lab are a freeze-dried, or “lyophilized,” formulation. “A clinician would simply add water, and it is ready to inject,” Green said. Green thinks this freeze-dried gene-delivery nanoparticle could be easily manufactured on a large scale.

Co-investigator Alfredo Quinones-Hinojosa, a Johns Hopkins Hospital clinician-scientist and associate professor in the departments of Neurosurgery and Oncology at the Johns Hopkins School of Medicine, said he could imagine particles based on this technology being used in conjunction with, and even instead of, brain surgery. “I envision that one day, as we understand the etiology and progression of brain cancer, we will be able to use these nanoparticles even before doing surgery,” Quinones said. “How nice would that be? Imagine avoiding brain surgery all together!”

Currently, patients with glioblastoma, or brain cancer, only have a median survival of about 14 months, Green said. “Methods other than the traditional chemotherapy drugs and radiation—or in combination with them—may improve prognosis,” he said.

Gene therapy approaches could also be personalized, Green said. “Because gene therapy can take advantage of many naturally-existing pathways and can be targeted to the cancer type of choice through nanoparticle design and transcriptional control, several levels of treatment specificity could be provided,” Green said.

The nanoparticles self-assemble from a polymer structural unit, so fabrication is fairly simple, said Green. Finding the right polymer to use, however, proved to be a challenge. Lead author Stephany Tzeng, a PhD student in biomedical engineering in Green’s lab screened an assortment of formulations from a “polymer library” before hitting on a winning combination.

“One challenge with a polymer library approach is that there are many polymers to be synthesized and nanoparticle formulations to be tested. Another challenge is designing the experiments to find out why the lead formulation works so well compared to other similar polymers and to commercially available reagents,” Green said.

Tzeng settled on a particular formulation of poly(beta-amino ester)s specifically attracted to glioblastoma (GB) cells and to brain tumor stem cells (BTSC), the cells responsible for tumor growth and spread. “Poly(beta-amino ester) nanoparticles are generally able to transfect many types of cells, but some are more specific to GBs and BTSCs,” Tzeng said.

The nanoparticles work like a virus, co-opting the cell’s own protein-making machinery, but in this case, to produce a reporter gene (used to delineate a tumor’s location) or new cancer fighting molecule. “It is possible that glioblastoma-derived cells, especially brain tumor stem cells, are more susceptible to our gene delivery approach because they divide much faster,” Tzeng added.

Not only are the particles convenient to use, the team discovered that dividing cells continued to make the new protein for as long as six weeks after application. “The gene expression peaked within a few days, which would correspond to a large initial dose of a therapeutic protein,” said Green. “The fact that gene expression can continue at a low level for a long time following injection could potentially cause a sustained, local delivery of the therapeutic protein without requiring subsequent injection or administration. The cells themselves would act as a ‘factory’ for the drug.”

Once the nanoparticles release their DNA cargo, Tzeng said the polymer quickly degrades in water, usually within days. “From there, we believe the degradation products are processed and excreted with other cellular waste products,” Tzeng said.

Members of the Green Lab are now working on identifying the intracellular mechanism responsible for facilitating cell-specific delivery. “We also plan to build additional levels of targeting into this system to make it even more specific. This includes modifying the nanoparticles with ligands to specifically bind to glioblastoma cells, making the DNA cargo able to be expressed only in GB cells, and using a DNA sequence whose product is only effective in GB cells.”

So far, the team has only successfully transfected brain tumor stem cells using these nanoparticles in a plastic dish. The next step is to test the particle in animal models.

“We hope to begin tests in vivo in the near future by implanting brain tumor stem cells into a mouse and injecting particles. We also hope to begin using functional genes that would kill cancer cells in addition to the fluorescent proteins that serve only as a marker,” Tzeng said.

Other authors who contributed to this work are Hugo Guerrero-Cázares, postdoctoral fellow in Neurosurgery and Oncology, and Joel Sunshine, an M.D.-Ph.D. candidate, and Elliott Martinez, an undergraduate leadership alliance summer student, both from Biomedical Engineering. Funding for this work came from the National Institutes of Health, Howard Hughes Medical Institute, the Robert Wood Johnson Foundation and a pilot-grant from Johns Hopkins Institute for NanoBioTechnology (INBT). Green is an affiliated faculty member of INBT. The research will be published in Issue #23 (August 2011) of the journal Biomaterials and is currently available online.

The Scientist magazine has announced its annual Multimedia Awards—the Labbys—and Johns Hopkins Institute for NanoBioTechnology’s video on collagen mimetic peptides has been selected as a finalist. According to the voting, we are a strong second in the race. It appears voting is continuing well past the original June 30 deadline. So keep voting!

Help choose us as the top science video by going to this website (http://the-scientist.com/2011/06/15/2011-labby-video-finalists/#vote) and selecting “Mimicking Collagen.” The video features Michael Yu, associate professor of materials science and engineering and some fantastic animations and illustration from INBT’s Animation studio. Animations in the video were created by Ella McCrea, a graduate from the Maryland Institute College of Art, and Nathan Weiss, a masters graduate from Johns Hopkins University.

Winners of the reader’s choice will be announced in the magazine and online in September. Top picks will also be chosen by The Scientist’s panel of judges, which includes the father of the infographic Nigel Holmes, Kirsten Sanford of the Science Channel (aka Dr. KiKi), Jeffrey Segall of the Albert Einstein College of Medicine in New York City, and David Kirby of the University of Manchester.

Johns Hopkins Institute for NanoBioTechnology (INBT) hosts the NanoBio Film Festival on June 29, 11 a.m. in Krieger 205. See the world premiere of three short videos made by members of INBT’s course on science communications. Free for Hopkins community.

Videos featured in this film festival describe the current research of students working in INBT affiliated laboratories. Students in the course learn how to communicate their work in nontechnical terms for general audiences. They work in teams to write, direct, film and produce the videos within a two-week time frame. The producers will be on hand to describe their experience making the videos and to answer questions.

The INBT film festival is part of the institute’s free professional development seminar series. Topics are geared toward undergraduate and graduate students.

Future seminars include:

July 13: Adam Steel, PhD, Director of Systems Engineering at Becton Dickinson, will discuss medical device development. Dr. Steel joined BD in 2005. Previously he was vice president of research and development at MetriGenix. He earned his PhD in analytical chemistry at the University of Maryland College Park and undergraduate degrees in chemistry and mathematics from Gettysburg College. He completed a postdoctoral fellowship in medical device development at the National Institutes of Standards and Technology.

July 27: Grant submission process and how to obtain funding; a roundtable discussion with INBT affiliated postdoctoral students.

For additional information on INBT’s professional development seminar series, contact Ashanti Edwards, INBT’s Academic Program Administrator at Ashanti@jhu.edu.

The war on cancer is fought on many fronts, even tiny, nanoscale ones. To train new scientists and engineers to combat the spread of cancer, Johns Hopkins Institute for NanoBioTechnology (INBT) has established a pre-doctoral (PhD) training program in Nanotechnology for Cancer Medicine. Together with the institute’s previously established Nanotechnology for Cancer Medicine postdoctoral fellowship, these two training programs will comprise the Johns Hopkins Cancer Nanotechnology Training Center (CNTC).

Similar to the postdoctoral program, the PhD training in nanotechnology for cancer medicine will educate graduate students to use nanotechnology solutions to diagnose, treat, manage, and hopefully one day, even cure cancer, said the CNTC’s director Denis Wirtz, the Theophilus H. Smoot professor of Chemical and Biomolecular Engineering in the Whiting School of Engineering.

The CNTC was funded by a $1.8 million grant over five years from the National Cancer Institute. Launched in the fall of 2010, the pre-doctoral training program has already attracted highly qualified students with bachelor’s degrees in diverse backgrounds such as biochemistry, genetics, molecular and cellular biology, as well as those who majored in engineering or physics. By attracting students with these sorts of educational backgrounds, Wirtz said, INBT will help develop what he calls “hybrid scientists, engineers, and clinicians.”

“We are seeking to train people who can develop new nanoscale materials and nanoparticles that will address biological functions related to the growth and spread of cancer, or metastasis, at a mechanistic level,” said Wirtz, who also directs INBT’s Engineering in Oncology Center and is INBT’s associate director.

Anirban Maitra, professor of pathology and oncology at the Johns Hopkins School of Medicine and co-director of the CNTC, said research will focus on the identification and preclinical validation of the most cancer-specific nanotechnology based therapies, particularly using the wealth of knowledge on the cancer genome emerging from CNTC participant scientists such as Kenneth Kinzler and Bert Vogelstein, both School of Medicine faculty.

Much like INBT’s other training programs, students seeking a doctorate specialization in nanotechnology for cancer medicine must jump through a few additional hoops than those students enrolled in traditional department-based pre-doctoral programs.

For example, in addition to the PhD requirements set forth by students’ home departments, CNTC fellows also complete two core nanotechnology courses, two intensive laboratory “boot camps”, one laboratory course designed to develop their skills in experimental and theoretical fundamentals in surface and materials science for biology and medicine, and one course in advanced cancer biology. Students must also complete two complementary laboratory rotations within their first year, participate in a professional development seminars, attend clinical conferences on cancer, among many other requirements. These extra steps set INBT trainees apart by giving them a more advanced skill set and making graduates more desirable in the job market, Wirtz said.

Generally, fellows take five to six years to complete the cancer nanotechnology for medicine PhD program. INBT will support CNTC trainees for two years, after which, the students will be funded by their primary departments from which their degrees will be conferred.

As many as six outstanding pre-doctoral fellows may enter the CNTC program per year. Candidates from under-represented groups in the science and engineering disciplines, including women and minorities, are encouraged to apply.

For more information about how to apply for the CNTC programs, please contact INBT’s Academic Program Administrator, Ashanti Edwards, at Ashanti@jhu.edu.

Blue and black, or white and gold? That is the question, apparently. Yes, we are still talking about The Dress, if you can believe it (even though we are secretly convinced that the white/gold camp is just having a laugh at our expense—it's clearly blue and black). To (ahem) shed some light on this great […]